Synapse - EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer

EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer Journal Article

Authors:	Oldrini, B.; Hsieh, W. Y.; Erdjument-Bromage, H.; Codega, P.; Carro, M. S.; Curiel-García, A.; Campos, C.; Pourmaleki, M.; Grommes, C.; Vivanco, I.; Rohle, D.; Bielski, C. M.; Taylor, B. S.; Hollmann, T. J.; Rosenblum, M.; Tempst, P.; Blenis, J.; Squatrito, M.; Mellinghoff, I. K.
Article Title:	EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer
Abstract:	Transport of macromolecules through the nuclear pore by importins and exportins plays a critical role in the spatial regulation of protein activity. How cancer cells co-opt this process to promote tumorigenesis remains unclear. The epidermal growth factor receptor (EGFR) plays a critical role in normal development and in human cancer. Here we describe a mechanism of EGFR regulation through the importin beta family member RAN-binding protein 6 (RanBP6), a protein of hitherto unknown functions. We show that RanBP6 silencing impairs nuclear translocation of signal transducer and activator of transcription 3 (STAT3), reduces STAT3 binding to the EGFR promoter, results in transcriptional derepression of EGFR, and increased EGFR pathway output. Focal deletions of the RanBP6 locus on chromosome 9p were found in a subset of glioblastoma (GBM) and silencing of RanBP6 promoted glioma growth in vivo. Our results provide an example of EGFR deregulation in cancer through silencing of components of the nuclear import pathway.
Keywords:	glioblastoma; breast-cancer; growth-factor receptor; pathway; cell-line; stat3; signaling network; transport; r package; own receptor
Journal Title:	Nature Communications
Volume:	8
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2017-12-01
Start Page:	2035
Language:	English
ACCESSION:	WOS:000417649500011
DOI:	10.1038/s41467-017-02185-w
PROVIDER:	wos
PMCID:	PMC5725448
PUBMED:	29229958
Notes:	Article -- Source: Wos